Rogier M. Klok

Meta-analysis: comparing the efficacy of proton pump inhibitors in short-term use

Background:  Proton pump inhibitors have a prominent role in the management of acid‐related diseases. Controlling expenses on proton pump inhibitors would yield great economic benefits for Dutch health care.

Direct Medical Costs of Serious Gastrointestinal Ulcers among Users of NSAIDs

BackgroundThe occurrence and prevention of gastrointestinal ulcers during use of NSAIDs has become a major healthcare issue.ObjectiveTo determine the direct medical costs of serious NSAID-related ulcer complications.MethodAn observational cost-of-illness study was conducted in a large general hospital serving a population of 152 989 persons. From November 2001 to December 2003 all consecutive patients hospitalised with serious NSAID-related ulcer complications were identified. Serious NSAID-related ulcer complications were defined as ulcerations of the stomach or proximal duodenum causing perforation, obstruction or bleeding that occurred during the use of NSAIDs, necessitating hospitalisation of the patient. Data were retrieved with respect to days hospitalised and the number and type of diagnostic and therapeutic interventions. The main outcome measure was estimated mean direct medical costs of resources used.ResultsA total of 104 patients were hospitalised with serious NSAID-related ulcer complications (incidence 31.4 per 100 000 persons per year). Most patients were elderly (mean 70.4 years, SD 16.7). In-hospital mortality was 10.6%. Mean direct medical costs were €8375 (95% CI 7067, 10 393). On the basis of these results, we estimated that approximately 5105 people are hospitalised with serious NSAID-related ulcer complications in The Netherlands each year, of whom 541 die in hospital. The total annual direct medical costs for serious NSAID-related ulcer complications in The Netherlands were estimated to be €42 754 375 (95% CI 36 077 035, 53 056 265).ConclusionsSerious NSAID-related ulcer complications have a mortality rate of 10.6% in The Netherlands and the annual direct medical costs to the country of such complications are approximately €42 750 000.

Towards a healthier discount procedure

Most national guidelines for pharmacoeconomic research prescribe discounting, mostly of money and health against the same rate. There is much debate on whether this is adequate. Two theoretical arguments, the consistency argument of Weinstein and Stason, and the paralyzing paradox of Keeler and Cretin, are mostly responsible for the current standards. However, more recently, several authors have indicated that the basis to claim the necessity of using similar discount rates is rather weak, both practically and theoretically. In terms of finding a new theoretical basis on which to base discount rates for money and, in particular, health, Van Hout has made an important suggestion arguing that the discount rate for health could be based on the expected growth in life expectancy and the diminishing marginal utility related to such additional health. Similarly, Gravelle and Smith argue that if the value of health grows over time, discount rates that are used for costs cannot directly be applied to effects, but should be adjusted downwards.

Switch patterns before and after patent expiry of omeprazole: a case study in The Netherlands

An increase of therapeutic substitution after patent expiry might have a negative effect on cost‐savings generated with newly introduced generic drugs. To evaluate influences of patent expiry on therapeutic substitution, switch behaviour before and after patent expiry was investigated.

Pharmacoeconomics of quetiapine for the management of acute mania in bipolar I disorder

Bipolar disorder (or manic depression) is a lifelong, severe and complex psychiatric illness characterized by recurrent episodes of depression and mania. The aim of this study is to explore the cost–effectiveness of quetiapine compared with other alternatives for the treatment of acute manic episodes in bipolar I disorder, with a specific focus on serious side effects. Four trials investigating quetiapine monotherapy and adjunctive therapy were performed to investigate the efficacy of quetiapine in patients with bipolar I disorder. Data were derived from The Netherlands Mental Health Survey and Incidence Study and used to construct a study population for the model. To assess the cost–effectiveness of quetiapine in the management of acute mania in bipolar I disorders, a discrete event simulation model of seven monotherapy and combination treatment options was developed. A comparison of the total costs demonstrates that all of the monotherapy options and placebo are more costly than the combination therapy options. The combinations of lithium with risperidone (€2365) and with olanzapine (€2429) are estimated to be less costly per patient than the combination of lithium with quetiapine (€2555). A group of 10,000 patients switching from olanzepine/lithium to quetiapine/lithium would involve extra costs of €1,260,000, but would prevent an estimated number of 362 serious side effects. Switching from risperidone/lithium to quetiapine/lithium would cost an additional €1,900,000 and would prevent 1580 serious side effects. In terms of serious side effects, the combination of lithium/quetiapine was superior to the combination of lithium with olanzapine or risperidone. It must be considered whether the decreased likelihood of developing a severe side effect is worth the extra costs incurred with the combination of quetiapine/lithium.

A Pharmacoeconomic Comparison of the Efficacy and costs of Pantoprazole and Omeprazole for the Treatment of Peptic Ulcer or Gastroesophageal Reflux Disease in the Netherlands

BACKGROUND The focus of treatment of patients with peptic ulcer or gastroesuphageal reflux disease has changed during the last 15 years, with a shift from histamine2-receptor antagonists to proton-pump inhibitors (PPIs). From 1993 to 2000, expenditures for omeprazole (90% of total market share of PPIs) increased in The Netherlands from 68 million euros to 230 million euros. In 1999, expenditures for pantoprazole accounted for the majority of the rest of the market share for PPIs. OBJECTIVE The objective of this study was to compare the efficacy and costs of treatment with pantoprazole and omeprazole in The Netherlands. METHODS First, we reviewed clinical studies that compared the efficacy of different dosages of omeprazole and pantoprazole. Second, we analyzed data from a nationwide database of drug prescriptions to determine the dosages used in daily practice in 1999. The data were based on a representative sample of approximately 40% of the Dutch community pharmacies. Third, we modeled the outcome of potential substitution of pantoprazole for omeprazole and the corresponding scenarios for nationwide cost savings using the prescription information from the nationwide database. Potential savings within the Dutch health care system were estimated. RESULTS The 1999 prescription data indicated that pantoprazole treatment cost a mean 1.59 euros/d, compared with 2.12 euros/d for omeprazole (1.00 euro = 1.0487 US dollars). The mean cost per defined daily dose of omeprazole was 1.65 euros, compared with 1.59 euros for pantoprazole. Following the summary of product characteristics, treatment with pantoprazole appeared to be less costly for all indications. The projected annual cost savings for substituting pantoprazole for omeprazole on 90% of treatment days were estimated at 40.8 million euros. However, these projected savings may be offset by the costs of switching and the costs of upward dose adjustments that some patients may require. CONCLUSIONS Based on the available documentation about effectiveness and costs of omeprazole and pantoprazole, pantoprazole may provide a more favorable pharmacoeconomic profile than omeprazole. However, this is only true if the substitution of omeprazole by pantoprazole can be achieved without loss of efficacy or tolerability.

Cost-effectiveness of a potential future Helicobacter pylori vaccine in the Netherlands : The impact of varying the discount rate for health

To estimate the cost-effectiveness of a potential Helicobacter pylori (HP) vaccine for the Dutch situation, we developed a Markov model. Several HP prevalence scenarios were assessed. Additionally, we assessed the impact of the discount rate for health on the outcomes, as this influence can be profound for vaccines. When applying the current discount rate of 1.5% for health, the expected cost-effectiveness of HP vaccination is estimated below the informal Dutch threshold of euro 20,000/LYG when the HP prevalence is assumed > or =20% in the Dutch population. In conclusion, we showed that HP vaccination could possibly be a cost-effective intervention. However, this depends to a large extend on the prevalence of HP in the population. Furthermore, we showed the large impact of the discount rate for health on the cost-effectiveness of a HP vaccination program, illustrative for other vaccination programs.

Continued utilization and costs of proton pump inhibitors after Helicobacter pylori eradication in chronic users of gastrointestinal drugs

SIRS, In the November issue of Alimentary Pharmacology and Therapeutics, Williams et al. suggested that many patients on eradication therapy for Helicobacter pylori require further anti-ulcer medications. They also suggested significant economic implications, without explicitly specifying these. Below, we present similar findings for The Netherlands and extend these with a formal cost analysis. We investigated the effect of H. pylori eradication on drug utilization and costs in chronic users of gastrointestinal drugs using drug dispensing data for 1994–99 from the InterAction Database. This database comprises prescription information for approximately 150 000 Dutch patients. We identified H. pylori eradication therapy as a prescription for a gastrointestinal drug (ATC 1⁄4 A02) and at least two prescriptions for antibiotics (ATC 1⁄4 J) on the same day. Chronic utilization of gastrointestinal drugs was defined as more than 0.5 DDD per day on average during the 4 months before eradication. To exclude non-steroidal anti-inflammatory drug (NSAID)-induced gastrointestinal drug utilization, patients with an NSAID prescription during at least 1 month in the year before eradication were excluded (n 1⁄4 11). Gastrointestinal drug costs were expressed in euros () per patient per month (1 1⁄4 £0.63) and were based on Dutch market prices (excluding value added tax). Calculations were performed for four periods: 4 months before eradication (I), first 4 months after eradication (II), 5– 8 months after eradication (III) and 9–12 months after eradication (IV). The t-test was used for statistical comparisons of different periods. We identified 161 H. pylori eradications, all using the internationally preferred regimen of a proton pump inhibitor, clarithromycin and amoxicillin. Overall, the percentage of patients on gastrointestinal drugs decreased with time since eradication (Table 1), with 40% non-users in period IV. The average costs for gastrointestinal drugs were 34 per patient per month before eradication (period I), but declined to 24 in period IV (P 1⁄4 0.002). However, average costs for proton pump inhibitors did not follow this trend, with no statistically significant differences in costs for periods IV and I. Less than half of gastrointestinal drug costs in the pre-eradication period were for proton pump inhibitors, whereas, after eradication, over 80% of gastrointestinal drug costs were for proton pump inhibitors. Gastrointestinal drug use was continued in pre-eradication proton pump inhibitor users, with only 30% of these cases becoming nonusers of gastrointestinal drugs in period IV. Proton pump inhibitor use was high amongst continued gastrointestinal drug users, representing 83% of the users and 90% of the costs in period IV. Of those persons not using proton pump inhibitors pre-eradication, but with continued gastrointestinal drug use in period IV, 60% became proton pump inhibitor users, accounting for 75% of gastrointestinal drug costs in period IV. Our analysis using a large-scale observational dataset shows continued use and costs of proton pump inhibitors after H. pylori eradication in chronic users of gastrointestinal drugs in The Netherlands. This is in line with the findings by Williams et al. for Ireland. In our study, overall gastrointestinal drug costs decreased after eradication, but 60% of eradicated patients still used gastrointestinal drugs — primarily proton pump inhibitors — 8–12 months after eradication. Several factors could explain this pattern. Firstly, therapy may have failed to eradicate H. pylori, which might be expected in about 20% of cases. Secondly, re-infection with H. pylori may take place after successful eradication, although this is very unlikely as re-infection rates are low. Finally, successful eradication of H. pylori may lead to an increased risk of gastrooesophageal reflux disease. Primary treatment for gastro-oesophageal reflux disease consists of proton pump inhibitors. Aliment Pharmacol Ther 2002; 16: 1033–1034.

Pharmacoeconomics of Helicobacter pylori: eradication versus maintenance therapy in controlling peptic ulcer disease

We performed an electronic search in Medline and EMBASE for papers comparing Helicobacter pylori eradication and H2RA-maintenance therapy in peptic ulcer. Treatment to eradicate H. pylori in patients with a proven ulcer has a favorable cost-effectiveness compared with maintenance therapy, with benefits for the patient and society. In most studies, it was assumed that no more gastrointestinal drugs were needed after eradication. Additional research is needed to provide empirical evidence on gastrointestinal drug utilization after eradication of H. pylori. The development of a vaccine against H. pylori remains however the ultimate goal in the fight against peptic ulcer disease.

Pharmacoeconomics of gastrointestinal drug utilisation prior and post Helicobacter pylori eradication

Background.  Eradication of Helicobacter pylori prevents recurrence of peptic ulcer. In pharmacoeconomic analyses it is often presumed that after successful eradication no more gastrointestinal drugs are used. We investigated this presumed positive monetary effect using General Practitioners prescribing data, including information in diagnosis.